Aluminum-Catalyzed Intramolecular Vinylation of Arenes by Vinyl Cations.

This study addresses the challenges associated with vinyl cation generation, a process that traditionally requires quite specific counterions. Described herein is a novel intramolecular vinylation of arenes catalyzed by aluminum(III) chloride, utilizing practical conditions and readily available vinyl triflates derived from 2-aceto-3-arylpropionates. Comprehensive experimental data support diverse carbocycle synthesis, exemplified by indenes and higher analogues. Control experiments verify the applicability of the vinylation protocol, and synthetic applications showcase a potent tubulin polymerization inhibitor with anticancer properties. Density functional theory computations reveal a Lewis-acid-driven mechanism involving triflate moiety abstraction to generate a reactive vinyl cation.

Transition structures for the oxy-ene reaction.

An overlooked pericyclic reaction between allyl alcohols and alkenes to form carbonyl compounds is analyzed. It combines the characteristic features of the Alder-ene reaction and of the oxy-Cope rearrangement. This oxy-ene reaction could be involved in biosynthetic pathways.

Regioselective Reductive Opening of Benzylidene Acetals with Dichlorophenylborane/Triethylsilane: Previously Unreported Side Reactions and How to Prevent Them.

Arylidene acetals are widely used protecting groups, because of not only the high regioselectivity of their introduction but also the possibility of performing further regioselective reductive opening in the presence of a hydride donor and an acid catalyst. In this context, the Et3SiH/PhBCl2 system presents several advantages: silanes are efficient, environmentally benign, and user-friendly hydride donors, while PhBCl2 opens the way to unique regioselectivity with regard to all other Brønsted or Lewis acids used with silanes. This system has been extensively used by several groups, and we have demonstrated its high regioselectivity in the reductive opening of 4,6- and 2,4-O-p-methoxybenzylidene moieties in protected disaccharides. Surprisingly, its use on 4,6-O-benzylidene-containing substrates 1 and 2 led to unreproducible yields due to the unexpected formation of several side products. Their characterizations allowed us to identify different pitfalls potentially affecting the outcome of reductive opening of arylidenes with the Et3SiH/PhBCl2 reagent system: alkene hydroboration, azide reduction, and/or Lewis acid-promoted cleavage of the arylidene. With this knowledge, we optimized reproducible and high-yielding reaction conditions that secure and extend the scope of the Et3SiH/PhBCl2 system as a reagent for the regioselective opening of arylidenes in complex and multifunctional molecules.

Alkynophilicity of Group 13 MX3 Salts: A Theoretical Study.

The concept of alkynophilicity is revisited with group 13 MX3 metal salts (M = In, Ga, Al, B; X = Cl, OTf) using M06-2X/6-31+G(d,p) calculations. This study aims at answering why some of these salts show reactivity toward enynes that is similar to that observed with late-transition-metal complexes, notably Au(I) species, and why some of them are inactive. For this purpose, the mechanism of the skeletal reorganization of 1,6-enynes into 1-vinylcyclopentenes has been computed, including monomeric ("standard") and dimeric (superelectrophilic) activation. Those results are confronted with deactivation pathways based on the dissociation of the M-X bond. The role of the X ligand in the stabilization of the intermediate nonclassical carbocation is revealed, and the whole features required to make a good π-Lewis acid are discussed.

From chitin to bioactive chitooligosaccharides and conjugates: access to lipochitooligosaccharides and the TMG-chitotriomycin.

The direct and chemoselective N-transacylation of peracetylated chitooligosaccharides (COSs), readily obtained from chitin, to give per-N-trifluoroacetyl derivatives offers an attractive route to size-defined COSs and derived glycoconjugates. It involves the use of various acceptor building blocks and trifluoromethyl oxazoline dimer donors prepared with efficiency and highly reactive in 1,2-trans glycosylation reactions. This method was applied to the preparation of the important symbiotic glycolipids which are highly active on plants and to the TMG-chitotriomycin, a potent and specific inhibitor of insect, fungal, and bacterial N-acetylglucosaminidases.

NIS-assisted aza-Friedel-Crafts reaction with α-carbamoysulfides as precursors of N-carbamoylimines.

A general and practical N-iodosuccinimide (NIS)-promoted aza-Friedel-Crafts reaction of various aromatic nucleophiles with N-acylimines generated in situ from α-amidosulfides to give a rapid access to highly functionalized amines is described. The newly developed methodology is very mild, fast, efficient, and complementary.

Highly enantioselective electrophilic α-bromination of enecarbamates: chiral phosphoric acid and calcium phosphate salt catalysts.

Metal-free chiral phosphoric acids and chiral calcium phosphates both catalyze highly enantio- and diastereoselective electrophilic α-bromination of enecarbamates to provide an atom-economical synthesis of enantioenriched vicinal haloamines. Either enantiomer can be formed in good yield with excellent diastereo- and enantioselectivity simply by switching the catalyst from a phosphoric acid to its calcium salt.

Sc(III)-doped zeolites as new heterogeneous catalysts: mukaiyama aldol reaction.

Sc(III)-doped solids based on zeolite materials have been investigated for the first time as catalysts in organic synthesis. Sc(III)-USY zeolite proved to be a novel and very efficient heterogeneous catalyst for the Mukaiyama aldol reaction. This easy-to-prepare catalyst exhibited wide scope and compatibility with functional groups and is very simple to use, easy to remove (by simple filtration), and is recyclable (up to three times without loss of activity).

"Click chemistry" in zeolites: copper(I) zeolites as new heterogeneous and ligand-free catalysts for the Huisgen [3+2] cycloaddition.

For the first time, copper(I)-exchanged zeolites were developed as catalysts in organic synthesis. These solid materials proved to be versatile and efficient heterogeneous, ligand-free catalytic systems for the Huisgen [3+2] cycloaddition. These cheap and easy-to-prepare catalysts exhibited a wide scope and compatibility with functional groups. They are very simple to use, easy to remove (by filtration), and are recyclable (up to three times without loss of activity). Investigations with deuterated alkynes and deuterated zeolites proved that this Cu(I)-zeolite-catalyzed "click" reaction exhibited a mechanism different from that reported for the Meldal-Sharpless version.

Synthesis of a neamine dimer targeting the dimerization initiation site of HIV-1 RNA.

A neamine dimer designed to bind to a specific sequence of HIV-1 RNA has been synthesized. Starting from neomycin B (1), a five-step synthesis efficiently provided a key protected neamine monomer 6 (28%). From the latter, coupling reactions with activated diacids gave dimers. After deprotection, a neamine dimer was obtained as the hexachlorohydrate salt 15 with 13% overall yield over nine steps.